Prithiviraj Jothikumar

Ph.D. Defense Presentation

Date: Thursday, July. 14th, 2016

Time: 2:00 PM

Location: IBB 1128, Suddath Seminar Room

Advisor:

Cheng Zhu, Ph.D. (Georgia Institute of Technology, BME)

Thesis Committee:

Arash Grakoui, Ph.D. (Emory University)

Hang Lu, Ph.D. (Georgia Institute of Technology, ChBE)

Manu Platt, Ph.D. (Georgia Institute of Technology, BME)

Krishnendu Roy, Ph.D. (Georgia Institute of Technology, BME)

Analysis of kinetic parameters on T cell recognition to viral infection

Following viral infections, antigen specific T cells play an important role in eliminating the virus from the host. Cytotoxic T cell expressing T cell receptors (TCR) plays a pivotal role in mediating the immune system by interacting with the viral antigen. The initial interaction between the two proteins determines whether to recognize or tolerate the antigen. Although it has been shown that viral mutations play a role in immune cell recognition, the mechanism of interaction and kinetics behind the impaired response has not been fully elucidated. By using a predominant antigenic epitope derived from cytomegalovirus (CMV) and using human CMV-specific T cells, the objective is to assess how certain amino acid “hotspot” mutation from the viral epitope influence TCR recognition to understand key parameters that underly the protective features of T cell response against CMV infection. Furthermore, as viral infections help shape the adaptive immune response, cytotoxic T cells undergo expansion to clear pathogens and then contract, during which some cells undergo apoptosis and others develop long-lived memory population for recall responses. Therefore, how this heterogeneity is established by the host is still unclear as distinct anatomical compartments within the spleen regulate T cell response uniquely. By using lymphocytic choriomeningitis virus (LCMV) mouse model, binding kinetics of T cells from distinct compartments provide an understanding on how T cell repertoire can be formed. Overall, this study focuses on explaining the kinetics of antigen recognition of various viral epitopes to antigen-specific CD8+ T cells mimicking viral infection using direct 2D binding assays such as biomembrane force probe (BFP) and micropipette adhesion frequency assay. As a result, this study aims to contribute advancing the field of virology and immunology.